| The objective of this study was to prepare a formulation of pranlukast hydrate( PLH) self- micro emulsions drug delivery system(SMEDDS) and to evaluate dissolution, properties and pharmacokinetics in rat. pranlukast hydrate was the first leukotriene receptor inhibitors,which shows very slight water solubility and present low oral bio-availability. In order to reduce increase the solubility of the drug, and enhance bio-availability of drug in vivo, PLH-SMEDDS was prepared.In this study, a ultraviolet spectrophotometry(UV) and high performance liquid chromatography( HPLC).The result of methodology shows good precision, accuracy and stability. Then, solubility, water partition coefficient, and stability were studied by the method as followed.Components of pranlukast hydrate SMEDDS were screened by solubility testing, Compatibility of different excipients and pseudo-ternary phase diagram. The optimal prescription was determined using the central composite design-response surface methodology. The observed values were close to predicted values. The central composite design-response surface methodology is useful for the formula optimization of pranlukast hydrate SMEDDS. In addition, using the optimized composition as standard, the factor of emulsifying was studied. The final formulations were ethyl oleate(22%), Cremophol EL( EL, 40%), triethanolamine( TEA, 10%) and anhydrous ethanol(18.0%), in which the content of PLH was 4%.The properties of PLH-SMEDDS were studied in order to make sure the quality of it. The surface morphology of PLH-SMEDDS was observed by transmission electron microscope. The particle size, PDI and Zeta potential of PLH-SMEDDS were determined by laser particle size analysis. The appearance of NMD-NLC was spheroidal with mean particle size of( 70.3±2.1nm)、( 85.9±2.2nm)、( 74.0±0.5nm) in the media of water, 0.1mol·L-1HCl and p H6.8 PBS respectively and the PDI of( 0.310±0.016)、( 0.320±0.015) and( 0.296±0.024) respectively. Zeta potential in water was-24.97±1.34 m V. The encapsulation efficiency of NMD-NLC were( 94.2±0.6%). Combine the particle size and visual method to evaluate the self emulsifying efficiency of PLH-SMEDDS. The result showed fast emulsifying, which formed micro-emulsion within 1min, and small particle size,which was around 70 nm.The HPLC method was developed for determination of PLH dissolution, which showed good in methodology. A dissolution method was founded to evaluate the release of drug from PLH-SMEDDS. And compare the dissolution of PLH-SMEDDS, pure PLH and physical mixture. At the same time, using model fitting method to instigate the dissolution property. The result showed that PLH-SMEDDS released 80% in 30 min. However, the pure PLH and physical mixture released below 30%. The dissolution showed that SMEDDS improve the dissolution rate of PLH.The HPLC methods were developed for the determination of PLH in rat plasma. The results of PLH-SMEDDS and pure PLH suspension after rats i.g. administration were compared. The pharmacokinetic parameter data was evaluated by statistical moment. The C max、AUC0-180、AUC0-∞ after administration of PLH-SMEDDS were 0.76, 2.72, 2.44 times, respectively, Compared with the pure PLH. By t-test, statistically significant differences were found in the main pharmacokinetic like C max、AUC0-180、AUC0-∞ between two groups indicating that to some extent PLH-SMEDDS can improve the drug concentration of rat plasma and increase the bio-availability. |
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